Dedicated Breast PET with [18F]Fluoroestradiol for Characterization of Estrogen Receptor-Positive Breast Cancers

According to the American Cancer Society, about two out of every three breast cancer cases are hormone receptor-positive. Most of these cases are estrogen receptor-positive (ER+), making this molecular subtype the most common type of breast cancer diagnosed today. The ER status in breast cancer is typically measured by immunohistochemistry (IHC) of fixed biopsy breast tissue. However, sampling error due to intratumoral heterogeneity1 presents a huge challenge in the overall tumor assessment. Non-invasive imaging plays a critical role to holistically characterize the whole tumor for more accurate diagnosis and staging.  

Positron emission tomography (PET), in particular, offers a highly sensitive quantitative measure of molecular markers expressed in tumors. Estradiol, a form of estrogen, is produced for tissues of the reproductive organs, and 18F-fluoroestradiol ([18F]FES) is a radiotracer that has been developed for PET imaging of ER status 2,3. Earlier clinical studies show that [18F]FES tumor uptake correlates with the level of ER expression in biopsy samples by IHC 4, and it also predicts the likelihood of response to endocrine treatment 5-8

Dedicated breast positron emission tomography (dbPET) (MAMMI, OncoVision, Spain) is an emerging imaging technique specific to the breast. At UCSF, I led a team of researchers to evaluate dbPET as an imaging tool to characterize the heterogeneity of primary breast tumors. More recently, we have extended the use of dbPET with [18F]FES to assess the ER expression in ER+ breast cancers and their response to neoadjuvant treatment 9. This study showed the potential of [18F]FES-dbPET imaging that may provide early readouts to gauge the likelihood of neoadjuvant treatment efficacy (see Figure 1). Future studies will be critical to further our understanding of [18F]FES uptake as a measure of ER functionality, providing clinical evidence to determine the optimal systemic therapy choice for ER+ breast cancer patients.

Figure 1. Examples of FES-dbPET for assessing treatment response. Top patient 1 with >90% ER+ ILC - A:  A 61-year-old female patient with grade 2 ER+ ILC in her right breast. FES-dbPET imaging at baseline with a SUVmax at 15.83 and total uptake volume at 15.72 cm3. B: FES-dbPET of the same patient after 2 months of treatment with letrozole showing a SUVmax at 6.11 and total uptake volume at 0.37 cm3. C: DCE-MRI after 3 months of treatment with letrozole, confirming the favorable response with no residual disease. Bottom patient 2 with >90% ER+ IDC - D:  A 49-year-old female patient with grade 2 ER+ IDC in her left breast. FES-dbPET imaging at baseline showed a SUVmax at 13.02 and total uptake volume at 12.60 cm3. E: FES-dbPET of the same patient after 3 weeks of treatment with non-ER targeted chemotherapy had a SUVmax at 16.26 but a reduced total uptake volume at 6.97 cm3 (45% reduction). F&G: DCE-MRI at baseline and after 3 weeks of treatment, confirming the tumor size reduction by 40%. (Source: npj breast cancer)


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7.            Linden HM, Stekhova SA, Link JM, et al: Quantitative fluoroestradiol positron emission tomography imaging predicts response to endocrine treatment in breast cancer. J Clin Oncol 24:2793-9, 2006

8.            Doroshow JH, Kummar S: Translational research in oncology--10 years of progress and future prospects. Nat Rev Clin Oncol 11:649-62, 2014

9.            Jones EF, Ray KM, Li W, et al: Initial experience of dedicated breast PET imaging of ER+ breast cancers using [F-18]fluoroestradiol. NPJ Breast Cancer 5:12, 2019

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